This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. DEVELOPMENT OF HIGH-PERFORMANCE DIGITAL IMAGING SYSTEMS FOR MESOSCALE IVEM APPLICATIONS. This effort focuses on research, and development to improve technologies for digital imaging as a replacement for film. This is an enabling technology for high-throughput, wide-field mesoscale data acquisition and computer-integrated microscopy. Specifically, we continue to refine the hardware and software employed with an 8k x 8k ultra-wide-field lens-coupled CCD camera system for production use in microscopy. After significant work in the development of direct detection devices (DDD), we continue to explore and develop new circuitry and radiation-hardened devices for use in TEM. Similarly, we continue engineering and software development activities to integrate emerging DDD prototypes for routine data acquisition on our resource IVEMs. As a driver for the continued development and refinement of these systems, we cultivate mesoscale microscopy applications that exploit the performance characteristics of these devices and apply them to collaborative research. These goals are organized into the following specific aims: first, in order to accommodate the need for ultra-wide-field high-throughput image acquisition, we continued to refine the control software and automation of the NCMIR 8k x 8k lens-coupled CCD camera system commissioned on our JEM4000#2, and the 4k x 4k lens-coupled CCD camera system commissioned on our JEM4000#1. Second, to more accurately record information about biological specimens, we continued to refine technologies to directly record images using radiation-hardened CMOS cameras invented at NCMIR, and to field these DDDs on a variety of key resource platforms. Third, we utilized the development and integrations knowledge obtained in fielding the DDD and the lens-coupled systems to perform a major detector upgrade to the Titan FEI 80-300 300keV STEM/TEM.